Test predicts heart attack risk

San Diego  Cardiovascular disease has long been the top killer in the Western world, but it’s hard to tell which patients are most at risk for a heart attack. San Diego-based GenWay Biotech has introduced a test it says can detect those patients as much as two to three years in advance.

The test measures three biological markers in the blood that indicate arterial plaque is becoming unstable and may rupture, said Thomas Silberg, GenWay’s president and chief executive. Doctors can then give these patients preventive care, Silberg said.

Called PREvent, the $95 test is meant for those who already have coronary artery disease. It distinguishes between those whose disease is stable and those at heightened risk of heart attack. The test, which must be ordered by doctors, is performed at GenWay’s laboratory.

The three biomarkers indicate the activity of independent molecular “pathways” linked to plaque rupture, indicating inflammation, stress and coagulation. The more pathways at work in a patient, the greater the chance of rupture.

GenWay, founded in 1998, employs 15 people. The company also sells an array of biological products, such as antibodies and other proteins, and provides services, such as product development and contract research.

Heart attacks characteristically occur in people whose arteries are narrowed by plaque, because they are more easily blocked by a blood clot. However, narrowed arteries don’t necessarily mean a heart attack will take place. So doctors have been looking for ways to reliably identify those most at risk.

PREvent was actively marketed for several months beginning in late 2011, in a pilot trial to assess doctor interest, Silberg said. The company ceased marketing the test until earlier this year, while it evaluated the results.

One finding was that doctors wanted to see independently reviewed evidence that the test has predictive power.

“We needed to have a peer-reviewed publication,” Silberg said. “We did not have one then. We do now.”

That study was published in May in the Journal of the American College of Cardiology. It found that when ranked for risk according to the biomarkers, the top 4 percent of patients had an 18.2 percent annual incidence of heart attack or death. That is five times the incidence of the bottom 34 percent least at risk.

The study was a collaboration between GenWay and independent researchers. They examined 3,415 patients with suspected or confirmed coronary artery disease undergoing cardiac catheterization.

The study’s 13-member team included two GenWay employees and two equity holders, and a fifth receiving consulting fees from GenWay. Two doctors from Emory University not compensated by GenWay, Danny J. Eapen and Arshed Quyyumi, said in the paper that they had full access to all data and took responsibility for the accuracy of the analysis.

The study was funded by three non-for-profits and the National Institutes of Health.

Another peer-reviewed study will soon be published, Silberg said.

The study was well-done and the results impressive, said Dr. Samir Damani, a cardiologist with Scripps Health who has also performed research on the mechanism underlying heart attacks.

“MI (heart attack) is associated with much higher rates of death than plain old coronary disease,” Damani said. “So the idea that there are biomarkers available that can help predict plaque rupture is not only a good concept, but it’s something that we’ve been after for many decades. It’s really the Holy Grail, how to predict plaque rupture.”

However, further studies are needed to confirm the results, he said.

“It’s only one study, and risk factors are notoriously different from study to study,” Damani said. “You’re looking at a demographic that could change based on age, based on gender, based on ethnicity, based on other risk factor profiles.”

And even if the study holds up, there’s the question of what doctors can do with this information, Damani said.

Other research has found signs of impending heart attacks. One published last year in Science Translational Medicine linked imminent heart attack to the sloughing off of endothelial cells that line the interior of blood vessels in a study. This sloughing actually is the beginning of a heart attack, the study found, and can occur up to two weeks before symptoms appear. Damani was the study’s first author.